Dual Photochemistry of Benzimidazole

Monomers of benzimidazole trapped in an argon matrix at 15 K were characterized by vibrational spectroscopy and identified as 1H-tautomers exclusively. The photochemistry of matrix-isolated 1H-benzimidazole was induced by excitations with a frequency-tunable narrowband UV light and followed spectroscopically. Hitherto unobserved photoproducts were identified as 4H- and 6H-tautomers. Simultaneously, a family of photoproducts bearing the isocyano moiety was identified. Thereby, the photochemistry of benzimidazole was hypothesized to follow two reaction pathways: the fixed-ring and the ring-opening isomerizations. The former reaction channel results in the cleavage of the NH bond and formation of a benzimidazolyl radical and an H-atom. The latter reaction channel involves the cleavage of the five-membered ring and concomitant shift of the H-atom from the CH bond of the imidazole moiety to the neighboring NH group, leading to 2-isocyanoaniline and subsequently to the isocyanoanilinyl radical. The mechanistic analysis of the observed photochemistry suggests that detached H-atoms, in both cases, recombine with the benzimidazolyl or isocyanoanilinyl radicals, predominantly at the positions with the largest spin density (revealed using the natural bond analysis computations). The photochemistry of benzimidazole therefore occupies an intermediate position between the earlier studied prototype cases of indole and benzoxazole, which exhibit exclusively the fixed-ring and the ring-opening photochemistries, respectively.


Table of Contents
Page Bibliography Supporting bibliography on multiple medicinal and pharmaceutical applications of benzimidazole (BzIm), and overview of the publications dedicated to structural and spectroscopic characterization of BzIm S2 Figure S1.
Geometry and atom numbering scheme of 1H-benzimidazole S4 Figure S2.
Least squares linear fits of vibrational spectrum of 1H-benzimidazole S4 Table S1.
Definition of internal coordinates used in the normal mode analysis S5 Table S2.
Vibrational assignment of 1H-BzIm isolated in an Ar matrix at 15 K S6 Table S3.
Vibrational assignment of 4H-BzIm isolated in an Ar matrix at 15 K S7 Table S4.
Vibrational assignment of 6H-BzIm isolated in an Ar matrix at 15 K S8 Figure S3.
IRC profiles computed for the ring-closure reaction of anti-and synisomers of Imino-Nitrile-Ylide to 1H-benzimidazole S13 Figure S7.
An expanded version of Figure 5 of the main text S14 Figure S8.
Bond orders, natural spin densities, and spin isodensity surfaces computed for the anti-and syn-isomers of 2-isocyanoanilinyl radical S15 Table S6.
Computed potential energy barriers for H-atom scrambling around the closed-ring benzimidazole and reaction rates for H-atom tunneling S16 Table S7.
Structures and relative energies computed for the open-ring isocyanoaniline and its open-ring prototropic tautomers S16 Table S8.
Electronic, Zero-Point Corrected, and Gibbs Free Energies Computed for the Isomers Discussed in This Work S17 Table S9.
Comparison of IR spectra of 1H-BzIm computed at 20 theory levels with the experimental IR spectrum of matrix-isolated benzimidazole S26 References.
Supporting Information References S32 S4 Figure S1. Geometry and atom numbering scheme of 1H-benzimidazole used for the definition of internal coordinates (see Table S1). Color codes: bluenitrogen, greycarbon, whitehydrogen.

S12
Note on a minor ring-opening photochannel.
Just like in benzoxazole, the sole cleavage of the N1−C2 bond in benzimidazole would lead to a fleeting nitrile ylide species. The potential energy barrier height for the back-reaction from nitrile ylide (anti-imino) to benzimidazole, in the electronic ground state, is as low as 3.1 kJ mol −1 only ( Figure S6a) and this reaction should therefore be extremely fast. A second isomer, syn-imino nitrile ylide, is much more stable than the former, the barrier height preventing it from a fast decay back to benzimidazole is 28.6 kJ mol −1 ( Figure S6b). Such a species would manifest itself by a characteristic very strong IR absorption below 2000 cm −1 due to νas(CNC) mode 80 (predicted values for this mode in syn-imino nitrile ylide are 1959 cm −1 , 547.6 km mol −1 ), however no such photoproduct band was detected in this work (see Figure S7). Indirect evidence of the fleeting nitrile-ylide intermediate is the observation of absorptions around 2050-2020 cm −1 , a very characteristic spectral manifestation of the ketenimine moiety. [81][82][83][84] The (imino)-ketenimine (−C=C=NH) 27 is isomeric of (imino)-nitrile-ylide (−C=N=CH) 24 and may be formed via intermediacy of (imino)-spiro-azirine 25 and triplet (imino)vinyl-nitrene 26 (see Scheme S1), similarly as it was reported for the respective (oxo)-substituted isomers. 85 The antisymmetric stretching vibration of ketenimine νas(CCN) has an intrinsically huge infrared intensity (above 800 km mol −1 , see Figure S7) and, considering the intensity of its experimental counterpart, the respective isomer should account for no more than 1-2% of the total.
Scheme S1. Computed energies of the isomers of benzimidazole, on the minor ring-opening pathway leading from nitrile-ylide 24, via spiro-azirine 25 and triplet vinyl-nitrene 26, to ketenimine 27. S13 Figure S6. Intrinsic reaction coordinate profiles for the ring-closure reaction of (a) anti-Imino-Nitrile-Ylide and (b) syn-Imino-Nitrile-Ylide to 1H-benzimidazole computed at the B97-1/def2-TZVP level in Cartesian (non-mass-weighted) coordinates.  Figure S8. Structures of (a) anti and (b) syn (with respect to the N1H bond) 2-isocyanoanilinyl radicals optimized at the UB97-1/def2-TZVP level of theory. The adopted numbering of heavy atoms is inherited from the benzimidazole molecule and is shown in red. Left: The bond orders, computed using the Natural Resonance Theory (NRT), are shown in purple (for the bonds between the heavy atoms). The non-bonding orbital populations at the heavy atoms are shown in green. Right: Spin isodensity surface (isovalue ±0.01 e) for the two radical isomers. The values near the heavy atoms correspond to the computed atomic natural spin density values. Blue color stands for the α spin density ("+") and yellow for the  spin density ("-"). Element colors: Hwhite; Cgrey; Nblue. Table S6. Parameters of the potential energy barriers along the intrinsic reaction coordinate for the isomerization reactions depicted in Figure 7, and reaction rates for H-atom tunneling from the vibrational ground state.    a Absolute energies (in Hartree) computed at the B97-1/def2-TZVP level of theory. The two last columns indicate some parts of this work in which the respective structures are presented graphically. All structures listed in this table were optimized using tight convergence criteria and belong to true energy minima (have zero imaginary frequencies in the respective Hessian matrices). The respective optimized Cartesian coordinates are collected in Table S9.  Figure S9. Twenty model chemistries (5 methods × 4 basis sets) comparing computed infrared spectrum of 1H-BzIm with the experimental infrared spectrum of benzimidazole monomers isolated in an Ar matrix, shown in six spectral ranges.